May 13, 2025

Genome of near-extinct northern white rhino offers hope for reviving the species Breakthrough from Scripps Research, San Diego Zoo, Max Planck Institute and other collaborators paves way for stem cell-based reproduction.

May 13, 2025

LA JOLLA, CA The northern white rhinoceros is one of the rarest animals on Earth, with just two females left and no natural way for the species to reproduce. Now, an international team of scientists at Scripps Research, the San Diego Zoo Wildlife Alliance, Max Planck Institute for Molecular Genetics, and other collaborators have mapped the entire genome of a northern white rhino. This represents a crucial step toward bringing the critically endangered species back from the edge using advanced reproductive technologies.

The complete genome can be used as a reference to analyze the health of previously developed northern white rhinoceros stem cells. Eventually, those stem cells may be able to generate sperm and eggs to yield new rhinos. The genome was published on May 13, 2025, in PNAS.

Professor Emeritus Jeanne Loring posing with a northern white rhinoceros. Credit: Jeanne Loring What's so exciting about this milestone is that we're getting closer to being able to rescue animals that otherwise might go extinct during our lifetimes, says co-senior author Jeanne Loring, Professor Emeritus at Scripps Research and a research fellow at the San Diego Zoo Wildlife Alliance. This is great progress not only for white rhinos, but for the entire field of animal conservation.

The new effort combined cutting-edge DNA sequencing and genome mapping techniques to build a high-quality genome. Scientists used cells previously collected from a male northern white rhinoceros named Angalifu, who lived at the San Diego Zoo Safari Park until his death in 2014. At the time, his skin cells were cryopreserved in the San Diego Zoos Frozen Zoo .

We layered together multiple technologies to make the most accurate genomic map possible, says Loring. It's like the rhino version of the Human Genome Project.

This new genome also represents a vital tool toward saving the endangered species. In 2011, Loring's team created the first induced pluripotent stem cells from northern white rhinos. They have since, in collaboration with the San Diego Zoo, created other lines of stem cells from nine different individual northern white rhinos. These lab-grown cells have the ability to become any other cell type, including eggs and sperm that could potentially be used to create embryos.

Collaboration was integral to achieving this milestone, says Marisa Korody, a scientist in conservation genetics at the San Diego Zoo Wildlife Alliance. This high-quality reference genome is a key piece of the puzzle that helps us understand how the stem cells are functioning and guides our next steps in the genetic rescue process. None of it would be possible without the Frozen Zoo and the rhinos whose cells were preserved decades ago.

But one major hurdle has always been quality control. Without a reference genome, scientists didn't know whether any of those stem cells had picked up harmful mutations during lab growth a common problem in both human and animal stem cells. In the new research, Loring's team was able to use the new, complete genome to analyze the previously created stem cell lineages. They discovered that one of the most promising of the stem cell lines had a large chunk of DNA missing more than 30 million base pairs affecting over 200 genes, including those involved in reproduction and tumor suppression.

If we hadn't built this genome, we wouldn't have known that, adds Loring. We thought we had a good stem cell line, but it turns out it had a mutation that could have made it unsafe to use for reproduction. Now we can go back and screen all the others. This becomes the gold standard for deciding which cells to move forward with.

The new genome also settled lingering questions about how different northern and southern white rhinos really are. Some earlier data suggested significant DNA differences that might make it risky for southern white rhinos to be implanted with northern white rhino embryos. But updated comparisons show their genomes are strikingly similar, giving scientists confidence that southern white rhinos which are far more numerous can serve as surrogates without major complications.

For Loring, who's been working on this project since 2007, the new genome is a symbol of what's possible. Now that we have their genome, we can apply all the tools we've developed for humans CRISPR gene editing, reporter genes, everything to help rescue them.

The work also sets a powerful example for other endangered species, Loring says. Efforts to save hundreds of different endangered species from mammals and birds to plants and corals depend on careful biobanking like that being done by the Frozen Zoo.

The Frozen Zoo had the foresight to freeze actual cells from these animals, she says. That means we're not trying to recreate a species from scraps of ancient, damaged DNA. We have the real thing.

Ultimately, the goal is to grow healthy embryos and implant them into surrogate mothers, then raise the resulting calves in protected environments. It's not Jurassic Park, Loring is quick to point out, and it doesn't depend on gene editing or engineering.

We're not resurrecting a mystery species we're restoring one we still know intimately, she adds. The rhino is big, gentle and unforgettable. It's the perfect symbol for what science can do to fight extinction.

In addition to Loring, authors of the study, Genomic map of the functionally extinct northern white rhinoceros (Ceratotherium simum cottoni), were Gaojianyong Wang, Camilo Jose Hernandez-Toro, Alexander Meissner and Franz-Josef M ller of the Max Planck I

LINK:	https://www.scripps.edu/news-and-events/press-room/2025/20250513-lorin...
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